The dual role of epithelial-to-mesenchymal transition in chronic allograft injury in pediatric renal transplantation.

摘要

BACKGROUND: Tubulointerstitial damage (TID) is a key feature of chronic allograft injury (CAI) and loss. One proposed mechanism attributing to TID is epithelial-to-mesenchymal transition (EMT); however, it has recently been shown to be unrelated to early TID in adult renal allografts. This has yet to be studied in late TID or in pediatric renal transplantation; both questions were investigated. METHODS: By using 83 unique pediatric renal transplant recipients, 126 protocol, serial, posttransplant renal biopsies were examined by centralized, blinded Banff grading for CAI and transcriptional profiling (AffyU133+2.0) at 3 (n=20), 6 (n=45), 12 (n=19), and 24 months (n=42). Two hundred forty-three EMT-associated genes, identified from the literature, were interrogated for their differential expression in biopsies with and without CAI, using standard bioinformatic algorithms. RESULTS: Early (3-6 months) enrichment of EMT (P